rs58582188

Variant names:

• chr10-8074288-A-AT
• rs58582188
• NM_001002295.2:c.*266dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001002295.2(GATA3):​c.*266dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 505,786 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (14 hom.)
• Consequence: GATA3 NM_001002295.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42
• Publications: 1 publications found

Genes affected

GATA3 (HGNC:4172): (GATA binding protein 3) This gene encodes a protein which belongs to the GATA family of transcription factors. The protein contains two GATA-type zinc fingers and is an important regulator of T-cell development and plays an important role in endothelial cell biology. Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia. [provided by RefSeq, Nov 2009]

GATA3 Gene-Disease associations (from GenCC):

• hypoparathyroidism-deafness-renal disease syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-8074288-A-AT is Benign according to our data. Variant chr10-8074288-A-AT is described in ClinVar as Likely_benign. ClinVar VariationId is 1201835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1948/151792) while in subpopulation AFR AF = 0.0298 (1233/41386). AF 95% confidence interval is 0.0284. There are 25 homozygotes in GnomAd4. There are 918 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1948 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002295.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	NM_001002295.2	MANE Select	c.*266dupT		3_prime_UTR	Exon 6 of 6	NP_001002295.1
	GATA3	NM_001441115.1		c.*266dupT		3_prime_UTR	Exon 6 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.*266dupT		3_prime_UTR	Exon 7 of 7	NP_001428045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.*266dupT		3_prime_UTR	Exon 6 of 6	ENSP00000368632.3
	GATA3	ENST00000346208.4	TSL:1	c.*266dupT		3_prime_UTR	Exon 6 of 6	ENSP00000341619.3
	GATA3	ENST00000461472.1	TSL:3	c.*545_*546insT		downstream_gene	N/A	ENSP00000515407.1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1947 AN: 151674 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.00780

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00265

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.00610 AC: 2159 AN: 353994 Hom.: 14 Cov.: 0 AF XY: 0.00591 AC XY: 1076 AN XY: 182164

African (AFR) AF: 0.0250 AC: 277 AN: 11094

American (AMR) AF: 0.0103 AC: 125 AN: 12192

Ashkenazi Jewish (ASJ) AF: 0.00817 AC: 96 AN: 11744

East Asian (EAS) AF: 0.00 AC: 0 AN: 27110

South Asian (SAS) AF: 0.00231 AC: 61 AN: 26384

European-Finnish (FIN) AF: 0.00297 AC: 71 AN: 23912

Middle Eastern (MID) AF: 0.0223 AC: 37 AN: 1656

European-Non Finnish (NFE) AF: 0.00588 AC: 1284 AN: 218296

Other (OTH) AF: 0.00963 AC: 208 AN: 21606

GnomAD4 genome AF: 0.0128 AC: 1948 AN: 151792 Hom.: 25 Cov.: 32 AF XY: 0.0124 AC XY: 918 AN XY: 74190

African (AFR) AF: 0.0298 AC: 1233 AN: 41386

American (AMR) AF: 0.0119 AC: 181 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00780 AC: 27 AN: 3460

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5146

South Asian (SAS) AF: 0.00209 AC: 10 AN: 4794

European-Finnish (FIN) AF: 0.00265 AC: 28 AN: 10550

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00630 AC: 428 AN: 67920

Other (OTH) AF: 0.0143 AC: 30 AN: 2102

Alfa AF: 0.00168 Hom.: 1

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58582188; hg19: chr10-8116251;